Arthritis drug less effective for obese patients

NEW YORK (Reuters Health) - Obese adults with rheumatoid arthritis may be less likely than thinner people to respond to some of the newer medications for the disease, a small study suggests.

The study, of 89 arthritis patients started on the drug infliximab (Remicade), found obese patients improved less than leaner ones.

Of the 15 obese patients, half were considered "responders" to 16 weeks of infliximab treatment -- meaning they showed a significant reduction in their scores on a standard measure of joint pain, swelling and levels of inflammation-related proteins in the blood.

In contrast, three-quarters of the 66 normal-weight and overweight patients were deemed responders, as were seven of the eight underweight patients.

Even when the researchers considered patients' symptom scores before starting treatment, body weight was still related to the likelihood of improvement.

The findings, published in the journal Arthritis & Rheumatism, raise the possibility that obese patients are less likely to see results with infliximab or other drugs in the same class, known as TNF blockers.

TNF blockers -- which also include the drugs etanercept (Enbrel), adalimumab (Humira) and golimumab (Simponi) -- work by inhibiting tumor-necrosis factor, an immune system protein that contributes to inflammation.

Rheumatoid arthritis is an autoimmune disease in which the immune system launches a misguided attack on the tissue lining the joints. TNF blockers are part of a group of relatively newer drugs known as biologic response modifiers, which are all designed to act on the immune system to help slow arthritis progression.

It is not clear why obese individuals might have less of a response to TNF blockers. But it's possible that inflammation-promoting proteins produced by fat tissue -- called adipocytokines -- could play a role, Dr. Paul P. Tak, one of the researchers on the new study, told Reuters Health in an email.

The explanation would not appear to rest in the drug itself, according to Tak, of the University of Amsterdam in the Netherlands.

Doses of infliximab, which is given intravenously, are adjusted according to patients' body weight -- which is why Tak's team focused on the drug for this study. So the lesser response among obese patients is unlikely to signal a need for a higher dose, the researchers say.

According to Tak's team, the study appears to be the first to look at how body weight might affect the response to TNF blockers, in patients with any autoimmune disease. (The drugs can also be used to treat certain other autoimmune diseases, such as the digestive disorders Crohn's disease and ulcerative colitis, and ankylosing spondylitis, a form of arthritis that affects the spine.)

So larger studies are still needed to confirm and extend the current findings. For now, they are interesting from a scientific point of view, Tak said, because they suggest that fat tissue could play a role in promoting the inflammation seen in RA.

For patients and doctors, he added, they serve as an alert that TNF blockers might be relatively less effective for obese people. In general, patients on anti-TNFs are expected to show a noticeable improvement within three to four months, after which alternative medications should be considered if there is no response.

Tak has served as a consultant to several drug companies, including Humira maker Abbott Laboratories and Wyeth, which makes Enbrel.